Site‐selective 8‐chloroadenosine 3′,5′‐cyclic monophosphate inhibits transformation and transforming growth factor α production in Ki‐ras‐transformed rat fibroblasts

Abstract

A site‐selective cAMP analog, 8‐chloroadenosine 3′,5′‐cyclic monophosphate (8‐Cl‐cAMP), was demonstrated to be a potent inhibitor of both the monolayer and soft agar growth of normal rat kidney (NRK) fibroblasts that had been transformed with the v‐Ki‐ras oncogene or treated with transforming growth factor α (TGFα). The growth inhibition was dose dependent and reversible and was accompanied by reversion of the transformed phenotype, suppression of TGFα production, and a decrease in p21ras protein levels. These effects of 8‐Cl‐cAMP were linked to the cAMP analog's selective modulation of the type I and type II cAMP‐dependent protein kinase regulatory subunits, RI and RII, present in Ki‐ras‐transformed and TGFα‐treated NRK cells.